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15.01.2001

Newsletter No. 7

The quality of the endometrium and the pregnancy rate in IVF With the advent of recombinant LH all of the sudden the two-cell theory of ovarian steroid biogenesis is back. Ovarian stimulation with FSH only or: Why not taking a little LH additionally. Selection of embryos without embryos Y chromosome analysis of infertile men and their sons conceived through intracytoplasmatic sperm injection 1.The quality of the endometrium and the pregnancy rate in assisted reproduction There is no doubt that successful assisted reproduction requires a receptive endometrium for implantation, nourishment and growth of the embryo. The usual control of the quality of the endometrium during the monitoring of the cycle consists in vaginal sonography and assessment of the thickness and the structure of the endometrium. It is often assumed that, at the time of HCG administration, a thin endometrium would correlate with a worse outcome of treatment than a thicker one. A recent large prospective study could not confirm this assumption. Similar conception rates were achieved with endometrial thickness ranging from about 7 to 11 mm. Since this study is based on a large number of patients and treatment cycles, it renders questionable older smaller studies that yielded different results. In one study there was a dependence of the pregnancy rate of the thickness of the endometrium in IVF treatment cycles but not in IVF/ICSI treatment cycles. Moreover, there are studies dealing with the endometrial perfusion and the pregnancy rate. Assuming that the endometrial thickness might depend upon the endometrial perfusion two treatment modes were tested: The administration of low-dose aspirin and transvaginal sildenafil (Viagra). In the Viagra-study only for treatment cases were reported and in the aspirin study the results were not unequivocal. Therefore, and under the aspect of the results of the above mentioned large study these studies do not provide therapeutic recommendations. Furthermore, other studies demonstrated that endometrial perfusion is not a predictive parameter with respect to pregnancy rate. An endometrium that is too thick, however, (more than 14 mm) and that is showing pathological alteration such as polyps has detrimental effects on the therapeutic outcome. References De Geyter, Schmitter M, De Geyter M, Nieschlag E, Holzgreve W, Schneider HPG (2000) Prospective evaluation of the ultrasound appearance of the endometrium in a cohort of 1,186 infertile women. Fertil Steril. 73: 106-113 Sher G, Fish JD (2000) Vaginal sildenafil (Viagra): a preliminary report on a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF Weissman A, Gotlieb L, Caspar RF (1999) The detrimental effect of increased endometrial thickness on implantation and pregnancy rates and outcome in a in vitro fertilization program. Fert. Steril. 71: 147-149 Yuval Y, Lipitz S, Dor J, Achiron R (2000) The relationship between endometrial thickness, and blood flow and pregnancy rates in in-vitro fertilization. Hum Reprod. 14: 1067-1071 Rinaldi L, Lisi F, Floccari A, Lisi R, Pepe G, Fishel S (1996) Endometrial thickness as a predictor of pregnancy after in-vitro fertilization but not after intracytoplasmatic sperm injection. Hum Reprod 11: 1538-1541 Wada I, Hsu CC, Williams G, Macnamee MC, Brinsden PR (1994) The benefits of low-dose aspirin therapy in women with impaired uterine perfusion during assisted conception. Hum. Reprod. 9:1954-1957 TOP 2. With the advent of recombinant LH all of the sudden the two-cell theory of ovarian steroid biogenesis is back. Ovarian stimulation with FSH only or: Why not taking a little LH additionally. The use of the (less expensive) urinary HMG preparations containing both, LH and FSH activity, was, in controlled ovarian stimulation following GnRH-agonist downregulation, rather outmoded in view of the availability of (more expensive) recombinant FSH preparations although the two-cell theory of ovarian steroid biogenesis was still valid. The new teaching was that LH is not required and may even be detrimental in controlled ovarian stimulation. In an excellent debate article the following conclusion is made: (i) there is no evidence-based clinical argument that the LH content of the available preparations for ovarian stimulation negatively affects the outcome of IVF treatments; (ii) it is possible that a substantial number of normogonadotropic women are profoundly down-regulated by standard GnRH agonist suppression, and could benefit from the addition of LH to their stimulation protocol; (iii) because there is no reliable or cost-effective way to detect which woman will need additional LH administration, it seems practical to systematically add LH to the ovarian stimulation protocols. Reference Levy DP, Navarro JM, Schattman GL, Davis OK, Rosenwaks Z (2000) The role of LH in ovarian stimulation. Exogenous LH: letā€™s design the future. Hum Reprod 15: 2258-2265 TOP 3. Selection of embryos without embryos Due to the legal situation in some countries the number of embryos that are allowed to be generated during a treatment cycle is limited to the number of three. Therefore, on the day after oocyte retrieval, when the oocytes have reached the pronuclear state, those three PNā€™s have to be selected for further embryo culture and the other PNā€™s might be kryopreserved. Up to recently no reliable criteria were available to choose the three good ones out of a set of zygotes. In view of the fact that only 30-40% of all fertilised oocytes attain the ability to implant this selection was nothing else but a lottery. In some other countries with a less strict legislation all available and good oocytes are allowed to develop to embryos and can be watched during embryo culture. Then, one or two embryos that show a normal development are selected and transferred into the uterus, which results in a high pregnancy rate without the risk of a triplet pregnancy. Now criteria are being elaborated that are increasingly reliable in determining the further growth potential of oocytes shortly after fertilization. A selection of the "good embryosā€¯ before they are embryos. A giant step for patients living in countries with a strict legislation. Reference Wittemer C, Bettahar-Lebugle K, Ohl J, Rongieres C, Nisand I, Gerlinger P (2000) Zygote evaluation: an efficient tool for embryo selection. Hum. Reprod. 15: 2591-2597 TOP 4. Y chromosome analysis of infertile men and their sons conceived through intracytoplasmatic sperm injection The Y chromosome is inherited from the father to the son. Thus, microdeletions on the Y chromosome that are associated with severely impaired spermatogenesis and require intracytoplasmatic sperm injection for parenthood may be transmitted to the son via ICSI. In order to study the prevalence of microdeletions in consecutive 86 men that required ICSI and fathered a son the Y chromosomes of the fathers and their sons were analysed for microdeletions. Fifty of the 86 men (56%) had idiopathic seminiferous tubule failure (STF); the remainder had a variety of other indications for ICSI. Deletions were found in two (6.9%) of 29 azoo- or severely oligospermic men with STF. Identical deletions were found in their respective sons. No de novo deletions were detected in the remaining 97 sons conceived by men without deletions. The study demonstrates that deletions on the Y chromosome are encountered only in very severe cases of STF and if deletions are observed in sons following ICSI they are transmitted vertically via ICSI. De novo deletions appear to be very rare. Reference Cram DS et al (2000) Y chromosome analysis of infertile men and their sons conceived through intracytoplasmatic sperm injection: vertical transmission of deletions and rarity of de novo deletions. Fertil Steril 74: 909-915 TOP

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